Convergence of heterotopic nociceptive information onto neurons of the subnucleus reticularis dorsalis in the rat

The nature of stimuli that activate neurones located within the Subnucleus Reticularis Dorsalis (SRD) was determined. These neurones do not respond to visual, auditory or proprioceptive stimuli but are preferentially or even exclusively activated by noxious stimuli applied to any part of the body; only neurones of a sub-group have a predominantly contralateral activation. All the neurones were exclusively activated by stimulation of A delta or A delta and C afferent fibres. These observations suggest that this well-delimited reticular structure is specifically involved in the processing of nociceptive information.     

Analysis of the recombination zone in hereditary persistence of fetal hemoglobin with fetal gene rearrangement of the G gamma-G gamma-A gamma type

An increased synthesis of fetal hemoglobin in adult life is a common feature of the genetically determined severe disorders like beta thalassemia and sickle cell anemia. A continued synthesis of fetal hemoglobin in adults is also characteristic of clinical or subclinical syndromes like respectively delta beta thalassemia or hereditary persistence of fetal hemoglobin (HPFH). These disorders are highly heterogeneous with respect to their molecular defects as well as to the composition of Hb F. We report here a novel case of hereditary persistence of fetal hemoglobin in heterozygous state discovered by chance, in a young perfectly healthy french man. The gamma chain of his fetal hemoglobin was almost entirely composed of G gamma chains. Molecular analysis of the DNA revealed the existence of triplicated gamma genes on one chromosome with the genotype arrangement of G gamma-G gamma-A gamma. A polymorphic Xmn I restriction site (at position -158 5' to the cap site) was present in 5' of both of these G gamma genes. The presence of this site in front of G gamma gene had previously been shown to be associated both with high G gamma phenotype constitutively and also with high fetal hemoglobin level only in case of anemic stress. In the absence of any anemic stress in this individual, the constitutive increase of both fetal hemoglobin and G gamma chains could be due to the presence of a chromosome with triplicated arrangement of gamma genes. The classical triplication (G gamma-A gamma-G gamma-A gamma) does not result in HPFH phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)     

Initial results and long-term clinical follow-up of an amorphous hydrogenated silicon-carbide-coated stent in daily practice

The hemocompatibility and biocompatibility of a stent are determined by the physical and electrochemical properties of the stent surface. The aim of this study was to determine the feasibility, safety and efficacy of implantation of a stent coated with silicon carbide. Baseline characteristics were collected prospectively. The occurrence of cardiac adverse events and the angina score were assessed at clinical follow-up. A total of 193 Tensum stents were implanted in 174 patients. In hospital, one patient experienced stent thrombosis and in 6% of the patients a creatinine kinase elevation to 240 U/l or more occurred. Long-term follow-up was performed in 172 patients, with a mean follow-up of 454 +/- 181 days. Ninety-seven per cent were still alive, 15% had undergone target-vessel revascularization, and 2% had angiographic restenosis and were treated with medication only. Seventy-one per cent of the patients were free of anginal complaints, and 20% had anginal complaints in Canadian Cardiac Society class I or II. The Tensum coronary stent showed to be a safe and efficacious device in this study, with a high primary success rate and favorable long-term clinical followup.     

Deletions within the mouse beta-globin locus control region preferentially reduce beta(min) globin gene expression

The mouse beta-globin gene cluster is regulated, at least in part, by a locus control region (LCR) composed of several developmentally stable DNase I hypersensitive sites located upstream of the genes. In this report, we examine the level of expression of the beta(min) and beta(maj) genes in adult mice in which HS2, HS3, or HS5,6 has been either deleted or replaced by a selectable marker via homologous recombination in ES cells. Primer extension analysis of RNA extracted from circulating reticulocytes and HPLC analysis of globin chains from peripheral red blood cells revealed that all mutations that reduce the overall output of the locus preferentially decrease beta(min) expression over beta(maj). The implications of these findings for the mechanism by which the LCR controls expression of the beta(maj) and beta(min) promoters are discussed.     

Ultra-High-Frequency Reprogramming of Individual Long-Term Hematopoietic Stem Cells Yields Low Somatic Variant Induced Pluripotent Stem Cells

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Pair-wise interactions of polymerization inhibitory contact site mutations of hemoglobin-S

The linkage of pair-wise interactions of contact site mutations of HbS has been studied using Le Lamentin [His-20 (α)→Gln], Hoshida [Glu-43 (β)→Gln] and α₂β₂^T87Q mutations as the prototype of three distinct classes of contact sites of deoxy HbS fiber. Binary mixture experiments established that β^A-chain with the Thr-87 (β)→Gln mutation is as potent as the γ-chain of HbF (α₂γ₂) in inhibiting polymerization. On combining the influence of Le Lamentin mutation with that of β₂^T87Q mutations; the net influence is only partial additivity. On the other hand, in binary mixture studies, combined influence of Hoshida mutation with that of β₂^T87Q mutations is synergistic. Besides, a significant level of synergistic complementation is also seen when the Le Lamentin and Hoshida mutations are combined in HbS (symmetrical tetramers). Le Lamentin and Hoshida mutation introduced into the cis-dimer of the asymmetric hybrid tetramer completely neutralizes the Val-6 (β) dependent polymerization. Accordingly, we propose that combining the perturbation of intra-double strand contact site with that of an inter-double strand contact site exhibit synergy when they are present in two different chains of the αβ dimer. A comparison of the present results with that of the earlier studies suggest that when the two contact site perturbations are from the same sub-unit of the αβ dimer only partial additivity is observed. The map of interaction linkage of the contact site mutations exposes new strategies in the design of novel anti-sickling Hbs for the gene therapy of sickle cell disease.